Semaglutide Use Could Prevent Up to 2 Million MACE in 10 Years, Model Suggests

Nearly 2 million major cardiac events could be avoided through the use of semaglutide at its indicated dose among eligible patients, according to the researchers of a new modeling study published in Diabetes, Obesity and Metabolism.1

While the modeling showed that semaglutide at a dose of 2.4 mg could significantly reduce the incidence of and death from major adverse cardiovascular events, known as MACE, the researchers warned that greater uptake of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) is needed to reach that mark. According to the researchers, uptake of treatment remains low even for target patients, such as those with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD).

Based on the model, over 3 million MACE were projected over the following 10 years, approximately 496,000 of which could be prevented with the use of semaglutide. | Image credit: peter hansen - stock.adobe.com

“Unfortunately, even in those with T2D for whom trials of GLP-1 RAs have consistently shown benefit and who are recommended for therapy by the American Diabetes Association, uptake of these therapies has been low,” the authors wrote. “Among patients with T2D and ASCVD, fewer than 15% of patients seen for routine care in 2021 were on a GLP-1 RA, suggesting that the cost of treatment, supply limitations, and difficulty in navigating payer approvals have limited uptake among those eligible by the FDA label indication.”

Among a group of patients with ASCVD, researchers of this new study developed Markov population–based predictive models to determine preventable MACE and cardiac deaths. The group identified 6 million adults with ASCVD in the United States, 40% (n = 3,054,781) of whom were estimated to potentially have at least 1 major cardiac event in the next decade in the absence of treatment to target it.

Patients included in the study had to meet inclusion criteria used in the randomized SELECT trial (NCT03574597), which determined that semaglutide reduced the risk of cardiac-related death compared with placebo among patients with preexisting cardiovascular disease.2 The SELECT trial led to the 2024 approval of semaglutide, marketed for weight loss as Wegovy, for the prevention of cardiovascular death, heart attack, and stroke in adults with cardiovascular disease and either obesity or overweight.3

There were 6.2 million adults in the United States meeting the criteria as of 2023, meaning they were aged 45 years or older, had a body mass index (BMI) of at least 27 kg/m2, and had known ASCVD without diabetes. Among these adults, the mean age was 67 years, the mean BMI was 32.6 kg/m2, more than half (56%) were male, and 71% were White.

Based on the model, over 3 million MACE were projected over the following 10 years, approximately 496,000 (95% CI, 216,999-786,815) of which could be prevented with use of semaglutide 2.4 mg, correlating to a 16% (95% CI, 7%-25%) relative risk reduction.

The reductions in cardiac events accounted for approximately 213,000 (95% CI, 91,913-346,427) avoided myocardial infarctions, approximately 110,000 (95% CI, 47,343-176,079) avoided strokes, and approximately 173,000 (95% CI, 75,582-276,539) avoided CV deaths.

Additional estimations from the model included over 2 million deaths from any cause, approximately 333,000 (95% CI, 199,867-485,798) of which would be avoided with semaglutide 2.4 mg.

Overall, more than 22 million adults in the United States are eligible for semaglutide based on its approved indications. Using the identified 16% risk reduction from the patients meeting SELECT criteria, the researchers determined that if all eligible patients took the treatment at the dose of 2.4 mg, over 2 million MACE and 1 million deaths could be prevented.

"Our model demonstrates a significant reduction in morbidity and mortality," the authors concluded. "Treatment with semaglutide 2.4 mg in eligible individuals could lead to a substantial prevention of cardiovascular events in the United States, regardless of age or severity of excess weight."

References

1. Nanna MG, Doan QV, Fabricatore A, et al. Population-level impact of semaglutide 2.4 mg in patients with obesity or overweight and cardiovascular disease: A modelling study based on the SELECT trial. Diabetes Obes Metab. Published online April 4, 2024. doi:10.1111/dom.16370
2. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. New Engl J Med. 2023;389:2221-2232.
3. FDA approved first treatment to reduce risk of serious heart problems specifically in adults with obesity or overweight. Food and Drug Administration. March 8, 2024. Accessed April 7, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-reduce-risk-serious-heart-problems-specifically-adults-obesity-or